Individualized pharmacotherapy for essential thrombocythemia using pharmacogenomic information
| Project/Area Number |
17K09943
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Meiji Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小松 則夫 順天堂大学, 医学部, 教授 (50186798)
荒木 真理人 順天堂大学, 医学(系)研究科(研究院), 先任准教授 (80613843)
今井 美沙 順天堂大学, 医学(系)研究科(研究院), 助教 (50709003)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アナグレリド / 本態性血小板血症 / non-responder / 個別化治療 / ヒドロキシウレア / JAK2遺伝子変異 / スタチン / 遺伝子変異 / 薬剤反応性 |
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| Outline of Final Research Achievements |
Although the use of Anagrelide (ANA) for essential thrombocythemia (ET) has been increasing, nearly 30% of patients may be non-responders. The goal of this study was to investigate factors associated with non-responders.
Demographic, clinical and genotypic (8 genes) factors were studied retrospectively in 120 ET patients. A non-responder was defined using the platelet reduction rate and the platelet count. Multivariate analyses were performed to identify the covariates affecting a non-responder. A total of 107 patients were included in the analyses, and 30 patients (28%) were non-responders. Pretreatment with hydroxyurea (HU) and hyperlipidemia for all patients and JAK2 mutation in patients without HU were significant covariates influencing a non-responder. Pretreatment with HU for all patients, and statin treatment and smoking history in patients without HU were covariates for ID50. All results indicated that HU and JAK2 mutation might reduce and statins increase the responses of ANA.
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| Academic Significance and Societal Importance of the Research Achievements |
アナグレリドは二次発がんリスクがないため、本態性血小板血症（ET）治療薬として有用性が高い。しかし、約30%の患者は本剤に不応答性を示す。本研究はカルテ調査を基に多変量解析により、ANA投与量と血小板減少効果の関係に影響する可能性のある因子（ヒドロキシウレアの治療歴、JAK2遺伝子変異とスタチンの併用）を明らかにした。
ANA不応答の影響因子について遺伝子情報を含めて詳細に検討した報告はこれまでになく、本研究は学術的意義が高い。更に、薬価が高いANAの治療効果の影響因子を同定できたことは、不応答による増量と副作用を回避できET治療薬の選択に利用できるため、医療経済の面からも有用性が高い。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Differences in warfarin pharmacodynamics and predictors of response among three racial populations.2019
Author(s)
Ohara M, Suzuki Y, Shinohara S, Gong IY, Schmerk CL, Tirona RG, Schwarz UI, Wen MS, Lee MTM, Mihara K, Nutescu EA, Perera MA, Cavallari LH, Kim RB, Takahashi H
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Journal Title
Clin Pharmacokinet
Volume: 印刷中
Issue: 8
Pages: 1077-1089
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: their influence on pharmacogenetic dosing algorithms.2017
Author(s)
K Kubo, M Ohara, M Tachikawa, LH Cavallari, MTM Lee, MS Wen, MG Scordo, EA Nutescu, MA Perera, A Miyajima, N Kaneko, V Pengo, R Padrini, YT Chen, H Takahashi.
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Journal Title
Pharmacogenomics J.
Volume: 17(6)
Issue: 6
Pages: 494-500
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Correlations between the enantio- and regio-selective metabolisms of warfarin.2017
Author(s)
Harumi Takahashi, Minami Ohara, Soichi Shibata, Ming Ta Michael Lee, Larisa H Cavallari, Edith A Nutescu, Maria G Scordo, Vittorio Pengo, Roberto Padrini, Koichiro Atsuda, Hajime Matsubara, Yuan Tsong Chen, Hirotoshi Echizen.
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Journal Title
Pharmacogenomics
Volume: 18(2)
Issue: 2
Pages: 133-142
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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